How is Kennedy disease (KD) treated?

Updated: Sep 30, 2019
  • Author: Paul E Barkhaus, MD, FAAN, FAANEM; Chief Editor: Nicholas Lorenzo, MD, MHA, CPE  more...
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Answer

No proven, effective treatment of Kennedy disease (KD) is available. However, the androgen-dependent nature of the disease is the rationale for use of anti-androgens, which have been shown to improve some aspects of the disease manifestations in patients.

The following is the summary of the relevant clinical trials performed in this area:

  • In a limited study of 2 patients, empiric therapy with high-dose testosterone failed to show consistent benefit. [75] Nevertheless, some rationale supports the use of testosterone in KD. [41]

  • Leuprorelin acetate is a luteinizing hormone-releasing hormone agonist. A phase 2, randomized, placebo-controlled trial of leuprorelin acetate in 50 patients with spinal and bulbar muscular atrophy for 48 weeks appeared to show some benefit based on cricopharyngeal opening duration (videofluorography) and reduced mutant AR accumulation (scrotal skin biopsy). [76] In an editorial on this trial, Fishbeck and Bryan cautioned on the results with respect to using cricopharyngeal opening duration as a surrogate marker. [77] A 48-week trial may also be too short given the chronicity of the disease.

  • From August 2006-March 2008, the Japan SBMA Interventional Trial for TAP-144-SR (JASMITT) was performed as a 48-week, randomized, double-blind trial with 204 patients. The authors concluded that treatment with leuprorelin did not show significant effects on swallowing function in patients with spinal and bulbar muscular atrophy, but leuprorelin was well tolerated. [78] While disease duration might influence the efficacy of leuprorelin, more clinical trials with sensitive outcome measures should be done. A 48-week trial may be too short given the chronicity of the disease.

  • In an another randomized, placebo-controlled trial using dutasteride (a 5alpha-reductase inhibitor) to inactivate testosterone no change was seen in the progression of muscle weakness or swallowing dysfunction in patients with Kennedy disease. [79]

  • In a review by Fishbeck, androgen-reducing strategies did not help control symptoms of KD. [80]

Other emerging therapeutic strategies tested in animal models include decreasing expanded polyglutamine androgen receptor expression, increasing degradation of the polyglutamine-expanded protein using heat shock protein 70, leading to misfolding of the mutant protein and elimination via the ubiquitin-proteasome system and autophagy mediated abnormal protein degradation. Improving mitochondrial function and providing trophic support to motor neurons and peripheral tissues using coenzyme Q10, idebenone, and growth factors have also been proposed. [81]

In an open trial using oral beta 2 agonist (clenbuterol), Querin et al found significant improvement in 6-minute walking distance and forced vital capacity at 12 months in 20 patients of KD (Class IV evidence). However, no difference in the Medical Council of Research (MRC) scores was noted preintervention and postintervention. Clenbuterol was well tolerated, except elevation of CK level and hand tremor in 2 subjects. The authors postulated an anaboliceffect of clenbuterol in preventing disease progression and recommended considering a trial with more widely available beta 2 agonist salbutamol in the future. [82]

Overall management of KD is directed at maintaining maximal function in the presence of this slowly progressive disease.

The severity and progression of illness should be monitored. Given the ongoing, slowly progressive weakness, assessing the patient's strength and tolerance to exertion, along with any compromise in activities of daily living or occupation, is important. Such periodic assessments allow for thoughtful, proactive management to minimize the patient's risk for falls, to optimize their mobility, and to provide for appropriate assistive devices as the disability increases.

Certification for disabled parking should be made when appropriate.


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